(82 days)
Not Found
No
The document describes a standard chemiluminescent immunoassay (CLIA) and its associated controls and calibrators. There is no mention of AI or ML in the intended use, device description, or performance studies. The analysis is based on a direct measurement of light signal proportional to the analyte concentration, which is a traditional immunoassay method.
No.
This device is an in vitro diagnostic immunoassay that quantifies parathyroid hormone levels, which are used for diagnosis, not for treating a disease or condition.
Yes.
The "Intended Use / Indications for Use" section explicitly states that "Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia resulting from disorders of calcium metabolism," indicating its use in diagnosing health conditions.
No
The device is an in vitro diagnostic (IVD) assay kit that includes reagents (antibodies, controls, calibration verifiers) and is intended to be used on a specific hardware analyzer (LIAISON® Analyzer). It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The DiaSorin LIAISON® 1-84 PTH assay is an in vitro chemiluminescent immunoassay (CLIA) intended for the quantitative determination of parathyroid hormone (1-84) in human serum and EDTA plasma."
It also states that the associated control and calibration verifier sets are "intended for in vitro diagnostic use".
These statements clearly indicate that the device is intended for use outside of the body to diagnose or aid in the diagnosis of a condition, which is the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The DiaSorin LIAISON® 1-84 PTH assay is an in vitro chemiluminescent immunoassay (CLIA) intended for the quantitative determination of parathyroid hormone (1-84) in human serum and EDTA plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia and hypocalcemia resulting from disorders of calcium metabolism. The test has to be performed on the LIAISON® Analyzer.
The DiaSorin LIAISON® 1-84 PTH Control Set is intended for in vitro diagnostic use as assayed quality control samples to monitor the accuracy and precision of the LIAISON® 1-84 PTH Assay.
The DiaSorin LIAISON® 1-84 PTH Calibration Verifiers are assayed quality control materials intended for in vitro diagnostic use in the quantitative verification of calibration and reportable range of the LIAISON® 1-84 PTH Assay.
Product codes (comma separated list FDA assigned to the subject device)
CEW, JJX
Device Description
The LIAISON® 1-84 PTH Assay is a modified two-step, two-site sandwich assay that uses two polyclonal antibodies for capture and detection of the 1-84 PTH molecule. Results are determined by a 2 point calibration conversion of the master curve to a working curve. The light signal is measured by a photomultiplier as relative light units (RLU) and is proportional to the concentration of 1-84 PTH present in the calibrators, controls or samples.
LIAISON® 1-84 PTH Control set contains;
- 2 levels controls containing human plasma spiked with 1-84 PTH, and . preservatives: 4 vials each level; lyophilized
The target concentration for control level 1 is 30 pg/mL. The target concentration for control Level 2 is 260 pg/mL.
The range of concentrations of each control is reported on the certificate of analysis provided with each LIAISON® 1-84 PTH Control set.
LIAISON® 1-84 PTH Calibration Verifier set contains:
- 4 levels containing human plasma spiked with 1-84 PTH, with preservative, 1 vial. each level, lyophilized.
The target concentration for cal verifier A is 10 pg/mL. The target concentration for cal verifier B is 80 pg/mL. The target concentration for cal verifier C is 400 pg/mL. The target concentration for cal verifier D is 1450 pg/mL.
The range of concentrations of each calibration verifier is reported on the certificate of analysis provided with each LIAISON® 1-84 PTH Calibration Verifier set.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Method Comparison: A method comparison study was performed following CLSI EP9-A3. Results for 193 samples showed a slope of 0.9810 (95% CI: 0.9497 to 1.0204), intercept of -2.23 pg/mL (95% CI: -5.29 to -0.61), and a correlation coefficient (R) of 0.9812.
Sample Matrix Comparison: 188 matched patient sets of EDTA plasma and serum samples were tested. The Passing & Bablok regression analysis showed a slope of 1.0481 (95% CI: 1.03 – 1.08), intercept of 0.14 pg/mL (95% CI: -0.48 - 0.69), and R2 of 0.9981.
Reference Range: A study was performed with 125 EDTA plasma samples and 124 serum samples from apparently healthy adults (21-70 years old). Based on the parametric method with 95% Reference Limit:
EDTA Plasma: Median PTH 25.0 pg/mL, Observed Range 5.72 - 45.4 pg/mL.
Serum: Median PTH 25.2 pg/mL, Observed Range 5.68 - 47.8 pg/mL.
Precision: Precision testing was performed following CLSI Guideline EP5-A2 on 7 frozen EDTA plasma samples and 2 kit controls. Samples were tested in 2 replicates per run, 2 runs per day for 20 operating days on 1 LIAISON® Analyzer (160 replicate results per sample). Total %CV ranged from 3.8% to 10.4% for samples and 4.6% to 5.0% for controls. Calibration verifiers were tested for 20 days with 80 replicate results per verifier. Total %CV ranged from 5.2% to 8.2%.
Linearity: One sample pool of serum and EDTA plasma was diluted and analyzed.
Serum: Observed 1-84 PTH = 0.9992x = 0.0835; R2 = 0.9976.
EDTA plasma: Observed 1-84 PTH = 0.9679x - 3.328; R2 = 0.9971.
High Dose Hook Effect: No high dose hook effect was observed for 1-84 PTH concentrations measured up to 60,000 pg/mL.
Recovery Study: Five high and five low concentration EDTA plasma samples were analyzed. Defined ratios of mixed high and low samples were tested. Mean Recovery was 95%.
Analytical Specificity Cross-Reactivity Studies: Tested human PTH fragments and structurally similar proteins. % Cross Reactivity ranged from 0.00001% (C-Telopeptide) to 0.00105% (7 – 84 PTH).
Interference Studies: No significant interference (≥ ±10%) was observed with various endogenous and exogenous substances at specified concentrations.
Limit of Blank, Limit of Detection and Limit of Quantitation:
LOB: ≤ 0.5 pg/mL
LOD: / pg/mL (value missing in document)
LOQ: 4.0 pg/mL
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 862.1545 Parathyroid hormone test system.
(a)
Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia (abnormally high levels of calcium in the blood) and hypocalcemia (abnormally low levels of calcium in the blood) resulting from disorders of calcium metabolism.(b)
Classification. Class II.
0
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an image of three stylized human profiles facing to the right, stacked on top of each other.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
June 22, 2015
DIASORIN INC. CAROL DEPOUW REGULATORY AFFAIRS SPECIALIST 1951 NORTHWESTERN AVENUE STILLWATER MN 55082-1482
Re: K150879 Trade/Device Name: LIAISON® 1-84 PTH Assay LIAISON® 1-84 PTH Control Set LIAISON® 1-84 PTH Calibration Verifiers Regulation Number: 21 CFR 862.1545 Regulation Name: Parathvroid hormone test system Regulatory Class: II Product Code: CEW. JJX Dated: March 31, 2015 Received: April 1, 2015
Dear Carol Depouw:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
1
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Katherine Serrano -S
For: Courtney H. Lias, Ph.D.
Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K150879
Device Name LIAISON® 1-84 PTH Assay LIAISON® 1-84 PTH Control Set LIAISON® 1-84 PTH Calibration Verifiers
Indications for Use (Describe)
The DiaSorin LIAISON® 1-84 PTH assay is an in vitro chemiluminescent immunoassay (CLIA) intended for the quantitative determination of parathyroid hormone (1-84) in human serum and EDTA plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia resulting from disorders of calcium metabolism.
The test has to be performed on the LIAISON® Analyzer.
The DiaSorin LIAISON® 1-84 PTH Control Set is intended for in vitro diagnostic use as assayed quality control samples to monitor the accuracy and precision of the LIAISON® 1-84 PTH Assay.
The DiaSorin LIAISON® 1-84 PTH Calibration Verifiers are assayed quality control materials intended for in vitro diagnostic use in the quantitative verification of calibration and reportable range of the LIAISON® 1-84 PTH Assay.
Type of Use (Select one or both, as applicable)|X Prescription Use (Part 21 CFR 801 Subpart D)
| | Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
3
510(k) Summary
LIAISON® 1-84 PTH Assay LIAISON® 1-84 PTH Control Set LIAISON® 1-84 PTH Calibration Verifiers
This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92
1. 510(k) Number: K150879
-
- Applicant: Carol A. DePouw
DiaSorin Inc. 1951 Northwestern Avenue, P.O. Box 285, Stillwater, MN 55082-0285 Office Number: 651-351-5850; Fax Number: 651-351-5669 Email: carol.depouw@diasorin.com
- Applicant: Carol A. DePouw
- Date: March 26, 2015
4. Proprietary and Established Names:
LIAISON® 1-84 PTH Assay LIAISON® 1-84 PTH Control Set LIAISON® 1-84 PTH Calibration Verifiers
5. Requlatory Information:
LIAISON® 1-84 PTH Assay
Regulation Section: 21 CFR 862.1545 Classification: Class II Product Code: CEW Panel: Clinical Chemistry (75)
LIAISON® 1-84 PTH Control Set LIAISON® 1-84 PTH Calibration Verifiers
Requlation Section: 21 CFR 862.1660 Classification: Class I, reserved Product Code: JJX Panel: Clinical Chemistry (75)
6. Predicate Devices:
The predicate device used to demonstrate substantial equivalence to the LIAISON® 1-84 PTH Assay is the Scantibodies Laboratory, Inc. Whole PTH™ (1-84) Specific immunoradiometric (IRMA) assay previously cleared under (K001411).
4
The predicate device used to demonstrate substantial equivalence to the LIAISON® 1-84 PTH Control Set is the LIAISON® N-TACT® PTH Control Set previously cleared under K033426.
The predicate device used to demonstrate substantial equivalence to the LIAISON® 1-84 PTH Calibration Verifiers is the LIAISON® N-TACT® PTH Calibration Verifiers previously cleared under K093498.
7. Device Description:
The LIAISON® 1-84 PTH Assay is a modified two-step, two-site sandwich assay that uses two polyclonal antibodies for capture and detection of the 1-84 PTH molecule. Results are determined by a 2 point calibration conversion of the master curve to a working curve. The light signal is measured by a photomultiplier as relative light units (RLU) and is proportional to the concentration of 1-84 PTH present in the calibrators, controls or samples.
LIAISON® 1-84 PTH Control set contains;
- 2 levels controls containing human plasma spiked with 1-84 PTH, and . preservatives: 4 vials each level; lyophilized
The target concentration for control level 1 is 30 pg/mL. The target concentration for control Level 2 is 260 pg/mL.
The range of concentrations of each control is reported on the certificate of analysis provided with each LIAISON® 1-84 PTH Control set.
LIAISON® 1-84 PTH Calibration Verifier set contains:
- 4 levels containing human plasma spiked with 1-84 PTH, with preservative, 1 vial . each level, lyophilized.
The target concentration for cal verifier A is 10 pg/mL. The target concentration for cal verifier B is 80 pg/mL. The target concentration for cal verifier C is 400 pg/mL. The target concentration for cal verifier D is 1450 pg/mL.
The range of concentrations of each calibration verifier is reported on the certificate of analysis provided with each LIAISON® 1-84 PTH Calibration Verifier set.
8. Intended Use:
The DiaSorin LIAISON® 1-84 PTH Assay is an in vitro chemiluminescent immunoassay (CLIA) intended for the quantitative determination of parathyroid hormone (1-84) in human serum and EDTA plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia and hypocalcemia resulting from disorders of calcium metabolism.
The test has to be performed on the LIAISON® Analyzer.
5
The DiaSorin LIAISON® 1-84 PTH Control Set is intended for in vitro diagnostic use as assayed quality control samples to monitor the accuracy and precision of the LIAISON® 1-84 PTH Assay.
The DiaSorin LIAISON® 1-84 PTH Calibration Verifiers are assayed quality control materials intended for in vitro diagnostic use in the quantitative verification of calibration and reportable range of the LIAISON® 1-84 PTH Assay.
9. Indication(s) for Use:
Same as Intended Use
10. Substantial Equivalence Information:
A comparison of the similarities and differences between the LIAISON® 1-84 PTH Assay and the predicate Scantibodies Laboratory, Inc. Whole PTH™ (1-84) Specific (IRMA) assay are provided in the following table:
Assay Similarities and Differences | ||
---|---|---|
Characteristic | Candidate Device | |
LIAISON® 1-84 PTH Assay | Predicate Device | |
Whole PTH™ (1-84) Specific | ||
Scantibodies Laboratory Inc. | ||
(K001411) | ||
Intended Use | intended for the quantitative | |
determination of parathyroid | ||
hormone (1-84) | intended for the in vitro | |
quantitative determination of | ||
human whole parathyroid | ||
hormone (PTH) | ||
Measured Analyte | Parathyroid Hormone (whole | |
molecule) | Parathyroid Hormone (whole | |
molecule) | ||
Assay Type | Chemiluminescent Immunoassay | Immunoradiometric |
(IRMA) assay | ||
Antibody | Goat polyclonal | Goat polyclonal |
Sample Matrix | EDTA Plasma and Serum | EDTA plasma |
Sample size | 150μL | 200μL |
Sample | ||
Handling/Processing | Automated | Manual |
Calibrators | 2 levels | |
Included with kit | 7 levels | |
included with kit | ||
Calibration Interval | Two-point calibration curve | |
stable for 7 weeks | 7 calibrator levels tested | |
with every assay | ||
Measuring range | 4 - 1800 pg/mL | 0 - 2300 pg/mL |
Reference range | EDTA Plasma: 5.72 – 45.4 pg/mL | |
Serum: 5.68 – 47.8 pg/mL | EDTA Plasma: 5 - 39 pg/mL |
6
Control Similarities and Differences | ||
---|---|---|
Characteristic | Candidate Device | |
LIAISON® 1-84 PTH Control Set | Predicate Device | |
LIAISON® N-TACT® PTH | ||
Control Set (K033426) | ||
Intended Use | intended for use as assayed quality | |
control samples to monitor the | ||
accuracy and precision of the | ||
LIAISON® 1-84 PTH | intended for use as assayed quality | |
control samples to monitor the | ||
accuracy and precision of the | ||
LIAISON® N-TACT® PTH | ||
Storage | Store at 2-8°C until ready to use | Same |
Levels | 2 levels: lyophilized | |
Level 1 (approx 30 pg/mL) | ||
Level 2 (approx 260 pg/mL) | 2 levels: lyophilized | |
Level 1 (approx 60 pg/mL) | ||
Level 2 (approx 560 pg/mL) |
Calibration Verifiers Similarities and Differences | ||
---|---|---|
Characteristic | Candidate Device | |
LIAISON® 1-84 PTH | ||
Calibration Verifiers | Predicate Device | |
LIAISON® N-TACT® PTH | ||
Calibration Verifiers (K093498) | ||
Intended Use | assayed quality control materials | |
intended for the quantitative | ||
verification of calibration and | ||
reportable range of the | ||
LIAISON® 1-84 PTH Assay | assayed quality control materials | |
intended for the quantitative | ||
verification of calibration and | ||
reportable range of the | ||
LIAISON® N-TACT® PTH | ||
Storage | 2 to 8°C | Same |
Levels | 4 levels; lyophilized | |
Cal Ver A (approx 10 pg/mL) | ||
Cal Ver B (approx 80 pg/mL) | ||
Cal Ver C (approx 400 pg/mL) | ||
Cal Ver D (approx 1450 pg/mL) | 4 levels; lyophilized | |
Cal Ver A (approx 20 pg/mL) | ||
Cal Ver B (approx 150 pg/mL) | ||
Cal Ver C (approx 350 pg/mL) | ||
Cal Ver D (approx 1500 pg/mL) | ||
Volume | 2.0 mLs | Same |
11. Standard/guidance Document Reference:
- CLSI Guideline EP5-A2, Evaluation of Precision Performance of Quantitative o Measurement Methods;
- CLSI Guideline EP6-A, Evaluation of Linearity of Quantitative Analytical Methods; o
- CLSI Guideline EP7-A2, Interference Testing in Clinical Chemistry: o
- CLSI Guideline EP9-A3, Measurement Procedure Comparison and Bias Estimation o Using Patient Samples; Approved Guideline;
- CLSI Guideline EP17-A2, Evaluation of Detection Capability for Clinical o Laboratory Measurement Procedures;
- CLSI Guideline C28-A3, Defining, Establishing and Verifying Reference Intervals o in the Clinical Laboratory.
12. Performance Characters:
Method Comparison
A method comparison study was performed following CLSI EP9-A3, mean of the duplicate results for the Scantibodies Laboratory Inc. Whole PTH™ (1-84) Specific and
7
singlicate results for the LIAISON® 1-84 PTH Assay were plotted. Passing & Bablok linear regression analyses were performed and gave the following results:
Passing & Bablok Fit | |||||
---|---|---|---|---|---|
n | Slope | 95% | |||
Confidence | |||||
Interval | Intercept | ||||
pg/mL | 95% Confidence | ||||
Interval | Correlation | ||||
coefficient (R) | |||||
193 | 0.9810 | 0.9497 to 1.0204 | -2.23 | -5.29 to -0.61 | 0.9812 |
Sample Matrix Comparison
One Hundred Eighty-eight (188) matched patient sets of EDTA plasma and serum samples were tested to determine if these sample types provide equivalent results on the LIAISON® 1-84 PTH Assay.
The following Passing & Bablok regression analyses results were obtained:
| EDTA plasma vs. | Slope | 95% CI | Intercept
pg/mL | 95% CI | R2 |
|-----------------|--------|-------------|--------------------|--------------|--------|
| Serum | 1.0481 | 1.03 – 1.08 | 0.14 | -0.48 - 0.69 | 0.9981 |
Reference Range
It is recommended that each laboratory establish its own range of expected values.
To assess the expected reference range for the LIAISON® 1-84 PTH Assay, a study was performed with 125 EDTA plasma samples (91 females and 34 males) and 124 serum samples (90 females and 34 males) collected from apparently healthy adults; 21 - 70 years of age, from mixed ethnic backgrounds (32.0% dark-skinned, 67.2% lightskinned and 0.8% unknown) with normal 25 OH Vitamin D. TSH, Total Calcium, Phosphorus, Magnesium, Creatinine and Alkaline Phosphatase levels from the northern and southern regions of the U.S. Based on the parametric method with 95% Reference Limit, the following values were established following CLSI guideline C28-A3.
| Population
United States | N | Median
PTH (pg/mL) | Observed Range
2.5th to 97.5th Percentile |
|-----------------------------|-----|-----------------------|----------------------------------------------|
| EDTA Plasma | 125 | 25.0 | 5.72 - 45.4 pg/mL |
| Serum | 124 | 25.2 | 5.68 - 47.8 pg/mL |
Precision
Precision testing was performed following CLSI Guideline EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline -Second Edition. A coded panel comprised of 7 frozen EDTA plasma samples spanning the assay range was prepared by DiaSorin Inc. One lot of LIAISON® 1-84 PTH controls (2 levels) were also tested in the study. The precision panel samples and kit controls were tested on two lots of LIAISON® 1-84 PTH in two replicates per run, 2 runs per day for 20 operating days on 1 LIAISON® Analyzer for a total of 160 replicate results per sample.
8
The 20 day results are summarized for the combined reagent lot numbers as sample mean PTH concentration in pg/mL, standard deviations and coefficient of variation (%CV) for between lot and Total across lots.
| | | Mean
PTH | Between-Lot | | Total (Across Lots) | |
|---------------|-----|-------------|-------------|------|---------------------|-------|
| Sample ID | n | (pg/mL) | SD | %CV | SD | %CV |
| Kit Control 1 | 160 | 30.2 | 1.02 | 3.4% | 1.52 | 5.0% |
| Kit Control 2 | 160 | 305.6 | 9.86 | 3.2% | 14.08 | 4.6% |
| EDTA PTH-S1 | 160 | 11.8 | 0.37 | 3.2% | 1.23 | 10.4% |
| EDTA PTH-S2 | 160 | 18.7 | 0.78 | 4.1% | 1.45 | 7.7% |
| EDTA PTH-S3 | 160 | 35.2 | 0.87 | 2.5% | 2.03 | 5.8% |
| EDTA S4-PTH | 160 | 176.5 | 5.67 | 3.2% | 6.69 | 3.8% |
| EDTA S5-PTH | 160 | 399.6 | 12.56 | 3.1% | 18.20 | 4.6% |
| EDTA S6-PTH | 160 | 1124.7 | 37.89 | 3.4% | 50.62 | 4.5% |
| EDTA S7-PTH | 160 | 1743.9 | 47.97 | 2.8% | 101.00 | 5.8% |
Combined lot precision
The calibration verifiers were tested on one LIAISON® Analyzer with one lot of LIAISON® 1-84 PTH Assay in two replicates per run, 2 runs per day for 20 operating days for a total of 80 replicate results per calibration verifier.
The mean, standard deviation, and coefficient of variation (%CV) of the results were computed for each of the tested calibration verifier levels.
| Sample ID | n | Mean
(pg/mL) | Intra-Run | | Run-to-Run | | Day-to-Day | | TOTAL
(Within-lot) | |
|----------------|----|-----------------|-----------|------|------------|------|------------|------|-----------------------|------|
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Cal Verifier A | 80 | 13.0 | 0.83 | 6.4% | 0.61 | 4.7% | 0.30 | 2.3% | 1.07 | 8.2% |
| Cal Verifier B | 80 | 87.2 | 3.58 | 4.1% | 2.81 | 3.2% | 0.00 | 0.0% | 4.52 | 5.2% |
| Cal Verifier C | 80 | 376 | 12.53 | 3.3% | 12.46 | 3.3% | 9.95 | 2.6% | 20.28 | 5.4% |
| Cal Verifier D | 80 | 1487 | 56.71 | 3.8% | 6.25 | 0.4% | 62.43 | 4.2% | 84.58 | 5.7% |
Calibration Verifiers 20 day precision
Linearity
One sample pool of each type: serum and EDTA plasma were diluted and analyzed by the LIAISON® 1-84 PTH Assay following CLSI EP6-A. The results were analyzed by a regression of Observed PTH Concentration versus Expected PTH Concentration.
The resulting equations for each sample type are: Serum: Observed 1-84 PTH = 0.9992x = 0.0835; R2 = 0.9976 EDTA plasma: Observed 1-84 PTH = 0.9679x - 3.328; R2 = 0.9971
High Dose Hook Effect
Testing was conducted to determine if the LIAISON® 1-84 PTH Assay is susceptible to artificially low results in the presence of very high levels of PTH (Hook Effect). Three serum and 3 EDTA plasma samples were spiked with 1-84 PTH to equal several concentrations above the assay measuring range of 1800 pg/mL. The spiked samples were measured in triplicate.
9
No high dose hook effect was observed for 1-84 PTH concentrations measured up to 60,000 pg/mL.
Recovery Study
Five (5) high concentration EDTA plasma samples and 5 low concentration samples EDTA plasma samples were analyzed neat on the LIAISON® 1-84 PTH Assay. Recovery samples were then prepared by mixing defined ratios of the high and low samples and tested in replicates of 5. The observed values were compared to the expected values to determine the % recovery.
| Sample | Defined
pg/mL | Expected
pg/mL | Observed
pg/mL | %
Recovery |
|---------------------|------------------|-------------------|-------------------|---------------|
| High Sample 1 (HS1) | 534 | | | |
| 2 HS1 : 1 LS1 | | 364 | 344 | 94% |
| 1 HS1 : 1 LS1 | | 277 | 262 | 95% |
| 1 HS1 : 2 LS1 | | 189 | 178 | 94% |
| Low Sample 1 (LS1) | 18.9 | | | |
| High Sample 2 (HS2) | 1088 | | | |
| 2 HS2 : 1 LS2 | | 734 | 713 | 97% |
| 1 HS2 : 1 LS2 | | 551 | 514 | 93% |
| 1 HS2 : 2 LS2 | | 368 | 331 | 90% |
| Low Sample 2 (LS2) | 13.8 | | | |
| High Sample 3 (HS3) | 457 | | | |
| 2 HS3 : 1 LS3 | | 311 | 300 | 97% |
| 1 HS3 : 1 LS3 | | 235 | 224 | 95% |
| 1 HS3 : 2 LS3 | | 159 | 153 | 96% |
| Low Sample 3 (LS3) | 12.7 | | | |
| High Sample 4 (HS4) | 45.2 | | | |
| 2 HS4 : 1 LS4 | | 32.2 | 31.3 | 97% |
| 1 HS4 : 1 LS4 | | 25.5 | 24.8 | 97% |
| 1 HS4 : 2 LS4 | | 18.8 | 18.6 | 99% |
| Low Sample 4 (LS4) | 5.74 | | | |
| High Sample 5 (HS5) | 1546 | | | |
| 2 HS5 : 1 LS5 | | 1045 | 990 | 95% |
| 1 HS5 : 1 LS5 | | 787 | 733 | 93% |
| 1 HS5 : 2 LS5 | | 529 | 501 | 95% |
| Low Sample 5 (LS5) | 28.2 | | | |
| | | Mean Recovery | | 95% |
Sample Equivalence:
One hundred Eighty-eight matched patient sets of EDTA plasma and serum with results spanning the assay range of the LIAISON® 1-84 PTH Assay were tested to determine sample equivalence.
Comparison of serum to EDTA plasma yielded the following equation: Serum = 1.0481x + 0.1438; R2 = 0.9981.
10
Analytical Specificity Cross-Reactivity Studies
Controlled studies of potentially cross-reacting substances were performed on the LIAISON® 1-84 PTH Assay. LIAISON® 1-84 PTH Specimen Diluent was spiked with the following human PTH fragments and structurally similar proteins at the concentrations listed below. Testing was based on CLSI EP-7A2.
| Cross-Reactant | Spiked
concentration | % Cross
Reactivity |
|-----------------------------|-------------------------|-----------------------|
| 7 – 84 PTH | 200,000 pg/mL | 0.00105% |
| 1 – 34 PTH | 200,000 pg/mL | 0.00005% |
| 13 - 34 PTH | 200,000 pg/mL | 0.00020% |
| 39 - 68 PTH | 200,000 pg/mL | 0.00090% |
| 44 – 68 PTH | 200,000 pg/mL | 0.00055% |
| 39 - 84 PTH | 200,000 pg/mL | 0.00050% |
| 53 - 84 PTH | 200,000 pg/mL | 0.00015% |
| Calcitonin | 200,000 pg/mL | 0.00008% |
| Osteocalcin | 200,000 pg/mL | 0.00005% |
| C-Telopeptide (β-crosslaps) | 200,000 pg/mL | 0.00001% |
Interference Studies
Controlled studies of potentially interfering endogenous substances performed in EDTA plasma at two PTH levels (40 and 70 pg/mL) showed no interference in the LIAISON® 1-84 PTH Assay at the highest spiked concentration for each substance listed below.
| Drug/Substance | Concentration at which no
significant interference
(≥ ±10%) was observed | | |
|--------------------------|--------------------------------------------------------------------------------|--|--|
| Hemoqlobin | 500 mg/dL | | |
| Bilirubin (conjugated) | 40 mg/dL | | |
| Bilirubin (unconjugated) | 20 mg/dL | | |
| Triglycerides | 3,000 mg/dL | | |
| Cholesterol | 500 mg/dL | | |
| Albumin | 12 a/dL | | |
| HAMA | 4,088 ng/mL | | |
| Rheumatoid Factor | 5,380 IU/mL | | |
11
Controlled studies of potentially interfering exogenous substances performed in EDTA plasma at two PTH levels (40 and70 pg/mL) showed no interference in the LIAISON® 1-84 PTH Assay at the highest spiked concentration for each substance listed below.
| Drug/Substance | Concentration at which no
significant interference
(≥±10%) was observed | |
|----------------------|-------------------------------------------------------------------------------|--|
| Acetaminophen | 20 mg/dL | |
| Acetylsalicylic Acid | 65 mg/dL | |
| Salicylic Acid | 60 mg/dL | |
| lbuprofen | 50 mg/dL | |
| Alendronate | 8 mg/dL | |
| Etidronate | 105 mg/dL | |
| Pamidronate | 18 mg/dL | |
| Risedronate | 6 mg/dL | |
| Vitamin D2 | 240 ng/mL | |
| Vitamin D3 | 240 ng/mL | |
| Calcitriol | 1 ng/mL | |
| Alfacalcidol | 2.5 µg/mL | |
| Biotin | 1 ug/mL | |
| Calcium Acetate | 40 mg/dL | |
| Calcium Citrate | 40 mg/dL | |
| Magnesium Chloride | 40 mg/dL | |
| Aluminum Sulfate | 40 mg/dL | |
| Lanthanum Chloride | 40 mg/dL | |
Limit of Blank, Limit of Detection and Limit of Quantitation
The Limit of Blank, Limit of Detection and Limit of Quantitation were determined according to CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline June 2012- Second Edition.
The following limits for serum and EDTA plasma were determined with the LIAISON® 1-84 PTH Assay:
LOB | LOD | LOQ |
---|---|---|
≤ 0.5 pg/mL | / pq/mL | 4.0 pg/mL |
12
Stability
Product | Storage Conditions | Claimed stability | |
---|---|---|---|
Reagent Integral | Open vial | on system | 28 days |
Reagent Integral | Open vial | 2-8°C | 28 days |
Open vial - Reconstituted | on system/RT | 2 hours | |
Calibrators | Open vial - | ||
Reconstituted and Frozen | -20°C | 8 weeks | |
Calibration curve | N/A | N/A | 7 days |
Open vial - Reconstituted | on system/RT | 2 hours | |
Controls | Open vial - | ||
Reconstituted and Frozen | -20°C | 8 weeks | |
Open vial - Reconstituted | on system/RT | 2 hours | |
Calibration Verifiers | Open vial - | ||
Reconstituted and Frozen | -20°C | 2 weeks |
Traceability
The LIAISON® 1-84 PTH Calibrators, Controls and Calibration Verifiers concentrations are referenced to an in-house standard preparation containing synthetic human PTH (1-84).
Value Assignment
Calibrators
A minimum of 5 vials of each level of calibrator are tested on a minimum of 3 LIAISON® Analyzers, using 2 different approved LIAISON®1-84 PTH Assay kit lots, in a minimum of 5 assay runs with 6 replicates per vial resulting in a minimum of 30 individual replicate results per calibrator level for final value assignment.
Controls
A minimum of 10 vials of each level of control are tested on a minimum of 3 LIAISON® Analyzers, using 2 different approved LIAISON® 1-84 PTH Assay kit lots, in a minimum of 5 assay runs over 10 days with four replicates per vial resulting in a minimum of 40 individual replicate results per control used for final value range assignment. The mean, standard deviation (sd) and % CV for each level of kit control is calculated and a ± 2SD range is established.
Calibration Verifiers
A minimum of 12 vials of each level of calibration verifier are tested on a minimum of 4 LIAISON® Analyzers, using 2 different approved LIAISON® 1-84 PTH Assay kit lots, in a minimum of 6 assay runs with four replicates per vial resulting in a minimum of 48 individual replicate results used per calibration verifier for final value range assignment. The mean, standard deviation (sd) and % CV for each level of calibration verifier is calculated and a ± 2SD range is established.
13
13. Conclusion:
The LIAISON® 1-84 PTH Assay, LIAISON® 1-84 PTH Control Set and the LIAISON® 1-84 PTH Calibration Verifiers are substantially equivalent in principle and performance to the Scantibodies Laboratory, Inc. Whole PTH™ (1-84) Specific immunoradiometric (IRMA) assay, the LIAISON® N-TACT® PTH Control Set and the LIAISON® N-TACT® PTH Calibration Verifiers, respectively.